Huntington's disease (HD) is a uniformly fatal, autosomal dominant neurodegenerative disorder. There is currently no treatment for this disease. Power calculations based on the current standard clinical assessments of HD, the Unified Huntington's Disease Rating Scale, indicate human clinical trials will have to involve hundreds of patients and run for several years in order to detect even a modest treatment benefit. The development of more sensitive and objective measurements of HD progression, termed HD biomarkers, are one path toward improving the efficiency of human clinical trials. Based on microarray studies on two mouse HD models and a small pilot study on human samples, we have identified a characteristic program of gene expression changes in skeletal muscle. This aim of this proposal is to develop muscle gene expression changes in HD biomarkers that will be more sensitive to disease progression than the current clinical rating scale.